Maternal human telomerase reverse transcriptase variants are associated with preterm labor and preterm premature rupture of membranes

Caroline Marrs, Kevin Chesmore, Ramkumar Menon, Scott Williams

Research output: Contribution to journalArticle

Abstract

Objective Premature aging and short telomere lengths of fetal tissues are associated with spontaneous preterm labor (PTL) and preterm premature rupture of membranes (pPROM). Maintenance of telomere length is performed by the enzyme telomerase. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase, and its dysfunction affects telomere shortening. This study assessed whether maternal or fetal genetic variations in the hTERT gene are associated with PTL or pPROM. Methods A case (PTL or pPROM) control (term birth) genetic association study was conducted in 654 non-Hispanic white mothers (438 term, 162 PTL, 54 pPROM) and 502 non-Hispanic white newborns (346 term, 116 PTB, 40 pPROM). Maternal and fetal DNA samples were genotyped for 23 single nucleotide polymorphisms (SNPs) within the hTERT gene. Allele frequencies were compared between cases and controls, stratified by PTL and pPROM. Maternal and fetal data were analyzed separately. Results Allelic differences in one SNP of hTERT (rs2853690) were significantly associated with both PTL (adjusted OR 2.24, 95%CI 1.64–3.06, p = 2.32e-05) and with pPROM (adjusted OR 7.54, 95%CI 3.96–14.33, p = 2.39e-07) in maternal DNA. There was no significant association between the hTERT SNPs analyzed and PTL or pPROM in the fetal samples. Conclusion hTERT polymorphisms in fetal DNA do not associate with PTL or pPROM risk; however, maternal genetic variations in hTERT may play a contributory role in risk of PTL and PPROM.

Original languageEnglish (US)
Article numbere0195963
JournalPLoS One
Volume13
Issue number5
DOIs
StatePublished - May 1 2018

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telomerase
RNA-directed DNA polymerase
Premature Obstetric Labor
labor
Mothers
Personnel
Membranes
Polymorphism
telomeres
single nucleotide polymorphism
Single Nucleotide Polymorphism
Nucleotides
Telomerase
DNA
Premature Rupture Fetal Membranes
Genes
Telomere Homeostasis
Term Birth
Premature Aging
Telomere Shortening

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Maternal human telomerase reverse transcriptase variants are associated with preterm labor and preterm premature rupture of membranes. / Marrs, Caroline; Chesmore, Kevin; Menon, Ramkumar; Williams, Scott.

In: PLoS One, Vol. 13, No. 5, e0195963, 01.05.2018.

Research output: Contribution to journalArticle

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abstract = "Objective Premature aging and short telomere lengths of fetal tissues are associated with spontaneous preterm labor (PTL) and preterm premature rupture of membranes (pPROM). Maintenance of telomere length is performed by the enzyme telomerase. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase, and its dysfunction affects telomere shortening. This study assessed whether maternal or fetal genetic variations in the hTERT gene are associated with PTL or pPROM. Methods A case (PTL or pPROM) control (term birth) genetic association study was conducted in 654 non-Hispanic white mothers (438 term, 162 PTL, 54 pPROM) and 502 non-Hispanic white newborns (346 term, 116 PTB, 40 pPROM). Maternal and fetal DNA samples were genotyped for 23 single nucleotide polymorphisms (SNPs) within the hTERT gene. Allele frequencies were compared between cases and controls, stratified by PTL and pPROM. Maternal and fetal data were analyzed separately. Results Allelic differences in one SNP of hTERT (rs2853690) were significantly associated with both PTL (adjusted OR 2.24, 95{\%}CI 1.64–3.06, p = 2.32e-05) and with pPROM (adjusted OR 7.54, 95{\%}CI 3.96–14.33, p = 2.39e-07) in maternal DNA. There was no significant association between the hTERT SNPs analyzed and PTL or pPROM in the fetal samples. Conclusion hTERT polymorphisms in fetal DNA do not associate with PTL or pPROM risk; however, maternal genetic variations in hTERT may play a contributory role in risk of PTL and PPROM.",
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